The present invention relates to the field of food intake modifiers, and more particularly to the field of modifiers that can be administered to increase or decrease mammalian food intake.
The physiology of the control of food intake is not well understood. Many cogent theories have been advanced based on data and observation. Several of these theories are discussed in "Physiology of the Control of Food Intake", Kissileff et al, Ann. Rev. Nutr., 2:371-418 (1982); Russek "Current Status of the Hepatostatic Theory of Food Intake Control", Appetite, 2:137-143 (1981); and Friedman et al, "The Physiological Psychology of Hunger: A Physiological Perspective", Physiological Review, 83(6):409-431 (1976). Notwithstanding the current knowledge in this area, the effect that the administration of any given substance will have upon a mammal's food intake is normally difficult if not impossible to predict in the absence of significant food intake data stemming from prior experience with that compound or substance.
The present invention relates in particular to the effects of a dichloro derivative of 2,5-anhydro-D-mannitol and its effect on the food intake behavior of mammals. 2,5-anhydro-D-mannitol is a known fructose analog. The literature contains several reports concerning the possible biochemical and/or metabolic effects of 2,5-anhydro-D-mannitol (hereinafter referred to as 2,5-AM). See Riquelme et al, "Mechanism of Action of 2,5- anhydro-D-mannitol in Hepatocytes", Journal of Biological Chemistry, 259(8):5115-5123 (Apr. 25, 1984); Stevens et al, "2,5-anhydro-mannitol Inhibits Gluconeogenesis from Dihydroxyacetone in Rat Hepatocytes", Fed. Proc. 42 (Part II) Abstract No. 2384 (1983); Stevens et al, "2,5-anhydro-D-mannitol Inhibits Glycogenolysis in Isolated Rat Hepatocytes", Fed. Proc. 40 (Part I) Abstract No. 3479 (1981); Hanson et al, "Hypoglycemic Effect of 2,5-anhydro-D-mannitol", Fed. Proc. 42 (Part II), Abstract No. 1453 (1983); Raushel et al, "The Substrate in Anomeric Specificity of Fructokinase", Journal of Biological Chemistry, 248 (23):8174-8177 (Dec. 10, 1973); Riquelme et al, "Inhibition by 2,5-anhydro-mannitol of Glycolysis in Isolated Rat Hepatocytes and in Ehrlich Ascites Cells", Proc. Natl. Acad. Sci. U.S.A., 82:78-82 (January, 1985) Riquelme, "Regulation of Carbohydrate Metabolism by 2,5-anhydro-D-mannitol", Proc. Natl. Acad. Sci. U.S.A., 80:4301-4305 (July, 1983); and Hanson et al, "Inhibition of Gluconeogenesis and Glycogenolysis by 2,5-anhydro-D-mannitol", Journal of Biological Chemistry, 259(1):218-223 Jan. 10, 1984). While most of these papers address the effect of 2,5-AM at cellular and intracellular levels, please note that Hanson et al (1984) discloses the administration of 2,5-AM to fasting mice and rats. Hanson et al fails to report any food intake data, nor does Hanson suggest what effect, if any, 2,5-AM might have in altering food intake.
Since 2,5-AM can be phosphorylated, one possible side effect of its use is ATP depletion. A need thus exists for substances to treat overeating or obesity, and/or anorexia or other conditions exhibiting a reduced appetite, which are less likely to exhibit undesirable side effects, such as ATP depletion.